TASOR expression in naive embryonic stem cells safeguards their developmental potential [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1090604 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28413300_1.fastq.gz | Fastqsanger.gz | |||
| SRR28413300_2.fastq.gz | Fastqsanger.gz | |||
| SRR28413301_1.fastq.gz | Fastqsanger.gz | |||
| SRR28413301_2.fastq.gz | Fastqsanger.gz | |||
| SRR28413302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:The seamless transition through stages of pluripotency relies on a delicate balance between transcription factor networks and epigenetic silencing mechanisms that ensure proper regulation of the developmental program, critical for normal development. Here, we uncover the pivotal role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in sustaining cell viability during the transition from naive to primed pluripotency, despite its rapid downregulation during this transition. Loss of TASOR in naive cells triggers replication stress, disrupts H3K9me3 heterochromatin formation, and compromise the transcriptional and post-transcriptional silencing of LINE-1 (L1) transposable elements (TEs), with these effects become more pronounced in primed cells. Remarkably, the survival of Tasor-knockout cells during naive to primed transition can be restored through the inhibition of cysteine-aspartic acid protease (Caspase) or deletion of mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to programmed cell death, specifically in cells exiting naïve pluripotency. Additionally, we propose that HUSH-promoted H3K9me3 in naïve PSCs sets the stage for ensuing DNA methylation in primed cells, establishing long-term silencing during differentiation. Our findings shed insights on the crucial impact of epigenetic programs established in early developmental stages on subsequent phases, underscoring their significance in the developmental process.
2024-09-16 | GSE262195 | GEO
Project description:The seamless transition through stages of pluripotency relies on a delicate balance between transcription factor networks and epigenetic silencing mechanisms that ensure proper regulation of the developmental program, critical for normal development. Here, we uncover the pivotal role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in sustaining cell viability during the transition from naive to primed pluripotency, despite its rapid downregulation during this transition. Loss of TASOR in naive cells triggers replication stress, disrupts H3K9me3 heterochromatin formation, and compromise the transcriptional and post-transcriptional silencing of LINE-1 (L1) transposable elements (TEs), with these effects become more pronounced in primed cells. Remarkably, the survival of Tasor-knockout cells during naive to primed transition can be restored through the inhibition of cysteine-aspartic acid protease (Caspase) or deletion of mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to programmed cell death, specifically in cells exiting naïve pluripotency. Additionally, we propose that HUSH-promoted H3K9me3 in naïve PSCs sets the stage for ensuing DNA methylation in primed cells, establishing long-term silencing during differentiation. Our findings shed insights on the crucial impact of epigenetic programs established in early developmental stages on subsequent phases, underscoring their significance in the developmental process.
2024-09-16 | GSE262194 | GEO
Project description:The seamless transition through stages of pluripotency relies on a delicate balance between transcription factor networks and epigenetic silencing mechanisms that ensure proper regulation of the developmental program, critical for normal development. Here, we uncover the pivotal role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in sustaining cell viability during the transition from naive to primed pluripotency, despite its rapid downregulation during this transition. Loss of TASOR in naive cells triggers replication stress, disrupts H3K9me3 heterochromatin formation, and compromise the transcriptional and post-transcriptional silencing of LINE-1 (L1) transposable elements (TEs), with these effects become more pronounced in primed cells. Remarkably, the survival of Tasor-knockout cells during naive to primed transition can be restored through the inhibition of cysteine-aspartic acid protease (Caspase) or deletion of mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to programmed cell death, specifically in cells exiting naïve pluripotency. Additionally, we propose that HUSH-promoted H3K9me3 in naïve PSCs sets the stage for ensuing DNA methylation in primed cells, establishing long-term silencing during differentiation. Our findings shed insights on the crucial impact of epigenetic programs established in early developmental stages on subsequent phases, underscoring their significance in the developmental process.
2024-09-16 | GSE262193 | GEO
Project description:TASOR expression in naive embryonic stem cells safeguards their developmental potential [CUT&TAG]
| PRJNA1090603 | ENA
Project description:TASOR expression in naive embryonic stem cells safeguards their developmental potential [ATAC-seq]
| PRJNA1090605 | ENA
Project description:The seamless transition through stages of pluripotency relies on a balance between transcription factor networks and epigenetic mechanisms. Here, we reveal the crucial role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in maintaining cell viability during the transition from naive to primed pluripotency. TASOR loss in naive pluripotent stem cells (PSCs) triggers replication stress, disrupts H3K9me3 heterochromatin, and impairs silencing of LINE-1 (L1) transposable elements, with more severe effects in primed PSCs. Notably, the survival of Tasor knockout PSCs during this transition can be restored by inhibiting caspase or deleting the mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to cell death specifically in cells exiting naive pluripotency. Our findings highlight the importance of epigenetic programs established in naive pluripotency for normal development.
| S-EPMC11646706 | biostudies-literature
Project description:Naive human pluripotent stem cells (hPSCs) represent a pre-implantation epiblast state able to efficiently differentiate into embryonic and extraembryonic pre-implantation lineages and to self-organise into blastocyst-like structures called blastoids. Naive hPSCs maintenance commonly relies on mouse embryonic fibroblast (MEFs), introducing variability and analytical confounders. Here, we describe a feeder-free culture system based on serum coating that supports long-term naive hPSC maintenance. Across five laboratories, 30 serum batches were evaluated for the expansion of 8 naive hPSC lines for up to 25 passages. Mass spectrometry identified fibronectin and collagens as extracellular matrix proteins consistently present in serum coating. Cells cultured on serum coating displayed growth kinetics, clonogenic capacity, mutation rates, and global gene expression profiles comparable to MEF-based cultures. Importantly, serum-cultured naive hPSCs efficiently underwent germ layer specification, retained trophectoderm competence, and generated blastoids with similar efficiency. Collectively, serum coating provides a scalable, cost-effective, and robust alternative to feeder-based systems, preserving genomic stability and developmental potential while eliminating MEF-associated disadvantages and variability. This platform facilitates large-scale applications of naive hPSCs and enables more reproducible mechanistic studies.
2025-12-22 | PXD059820 | Pride
Project description:Naive human pluripotent stem cells (hPSCs) represent a pre-implantation epiblast state able to efficiently differentiate into embryonic and extraembryonic pre-implantation lineages and to self-organise into blastocyst-like structures called blastoids. Naive hPSCs maintenance commonly relies on mouse embryonic fibroblast (MEFs), introducing variability and analytical confounders. Here, we describe a feeder-free culture system based on serum coating that supports long-term naive hPSC maintenance. Across five laboratories, 30 serum batches were evaluated for the expansion of 8 naive hPSC lines for up to 25 passages. Mass spectrometry identified fibronectin and collagens as extracellular matrix proteins consistently present in serum coating. Cells cultured on serum coating displayed growth kinetics, clonogenic capacity, mutation rates, and global gene expression profiles comparable to MEF-based cultures. Importantly, serum-cultured naive hPSCs efficiently underwent germ layer specification, retained trophectoderm competence, and generated blastoids with similar efficiency. Collectively, serum coating provides a scalable, cost-effective, and robust alternative to feeder-based systems, preserving genomic stability and developmental potential while eliminating MEF-associated disadvantages and variability. This platform facilitates large-scale applications of naive hPSCs and enables more reproducible mechanistic studies.
2025-12-22 | PXD072053 | Pride
Project description:Conventional human pluripotent stem cells (hPSCs) are widely used to study early embryonic development, generate somatic cells, and model diseases, with differentiation potential aligned to a post-implantation epiblast identity. In the past decade, naive hPSCs, representing a pre-implantation stage, have been derived, exhibiting broader differentiation potential, including embryonic and extraembryonic lineages such as trophectoderm, primitive endoderm, and extraembryonic mesoderm. Naive hPSCs can also self-organize into blastocyst-like structures called blastoids. However, their culture typically relies on mouse embryonic fibroblasts (MEFs), which are variable, resource-intensive, and can contaminate analyses. We report the long-term maintenance of naive hPSCs in a feeder-free, serum-coated system. Growth rate, clonogenicity, and gene expression profiles on serum coating were comparable to MEF-based cultures, but serum coating minimised fibroblast contamination. Naive hPSCs cultured on serum exhibited faster exit from pluripotency, more efficient germ layer specification, and retained trophectoderm potential with high blastoid formation efficiency. Exome sequencing revealed fewer mutations in serum-cultured cells, and mass spectrometry identified extracellular matrix proteins like vitronectin, fibronectin, and collagens in the serum coating. Overall, serum coating offers a scalable, cost-effective alternative for naive hPSC culture, maintaining developmental potential, reducing DNA mutations, and eliminating MEF-related confounding factors. We believe serum coating will expand the use of naive hPSCs to large-scale studies and mechanistic insights of developmental and disease modelling.
2025-12-22 | GSE287199 | GEO
Project description:Conventional human pluripotent stem cells (hPSCs) are widely used to study early embryonic development, generate somatic cells, and model diseases, with differentiation potential aligned to a post-implantation epiblast identity. In the past decade, naive hPSCs, representing a pre-implantation stage, have been derived, exhibiting broader differentiation potential, including embryonic and extraembryonic lineages such as trophectoderm, primitive endoderm, and extraembryonic mesoderm. Naive hPSCs can also self-organize into blastocyst-like structures called blastoids. However, their culture typically relies on mouse embryonic fibroblasts (MEFs), which are variable, resource-intensive, and can contaminate analyses. We report the long-term maintenance of naive hPSCs in a feeder-free, serum-coated system. Growth rate, clonogenicity, and gene expression profiles on serum coating were comparable to MEF-based cultures, but serum coating minimised fibroblast contamination. Naive hPSCs cultured on serum exhibited faster exit from pluripotency, more efficient germ layer specification, and retained trophectoderm potential with high blastoid formation efficiency. Exome sequencing revealed fewer mutations in serum-cultured cells, and mass spectrometry identified extracellular matrix proteins like vitronectin, fibronectin, and collagens in the serum coating. Overall, serum coating offers a scalable, cost-effective alternative for naive hPSC culture, maintaining developmental potential, reducing DNA mutations, and eliminating MEF-related confounding factors. We believe serum coating will expand the use of naive hPSCs to large-scale studies and mechanistic insights into developmental and disease modelling.
2025-12-22 | GSE284541 | GEO